Autoimmune Diseases

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Autoimmune Diseases

• Dr. Raid Jastania

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Autoimmune Diseases

• Group of diseases with common pathological
  process
• Presence of auto-antibody
• ?defect in B-cells or T-cells
• Genetic and Environmental etiological factors
• Result in failure of self-tolerance
• The process involve Ag-Ab binding and Ag-Ab
  complex formation
• Process may lead in complement activation and
  inflammation with tissue injury

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Autoantibody

• Failure to maintain self-tolerance
• Autoantibody can be formed to
• Nuclear antigen
• Cytoplasmic antigen
• Cell surface antigen
• Proteins and phospholipids

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Anti Nuclear Antibody (ANA)

• ANA represent diversity of antibodies that bind
  to several nuclear antigen
• Anti-DNA
• Anti-Histone
• Antibody to Non-Histone
• Antibody to nucleolar antigen
• ANA is usually detected by indirect
  immunofluorescence

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Anti Nuclear Antibody (ANA)

• Patterns of ANA staining
• Homogenous antibody to chromatin, histone or DNA
• Rim/Peripheral antibody to DNA
• Speckled antibody to histone (Sm,
  ribonucleoprotein RNP, SS-A (Ro), SS-B (La))
• Nucleolar pattern

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Systemic Lupus Erythematosus

• Autoimmune Disease
• Multi-system disease
• Variable behaviour, unpredictable, remitting
  relapsing, acute and gradual.
• May involve any organ
• Common Skin, kidney, serosal membranes, joints,
  heart.

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Systemic Lupus Erythematosus

• ANA (anti-DNA, anti-Sm, anti-phospholipid)
• Prevalence 1/2500 person
• Female male 91
• 1/700 women
• More common and severe in blacks (1/245)
• Onset 2nd or 3rd decade

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SLE Criteria for Diagnosis

• Malar Rash
• Discoid Rash
• Photosensitivity
• Oral ulcers
• Arthritis
• Serositis
• Renal disorder

• Neurologic disorder
• Hematologic disorder
• Immunologic disorder
• ANA

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SLE

• ANA is sensitive to SLE but not specific
• ANA is present in 5-15 of normal people
• More specific to SLE are
• Anti-DNA
• Anti-Sm
• LE bodies (hematoxylin bodies)
• Antiphospholipid 40-50 of cases
• Antiphospholipid syndrome (lupus anticoagulants)

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SLE Atiology

• Genetic factors
• 25 concordance in monozygotic twins
• Increase risk of disease in family members
• SLE and HLA-DQ association
• Some SLE patients have deficiency in complement
  components

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SLE Atiology

• Non-Genetic factors
• Lupus-like syndrome with drug admenistration,
  procainamide, hydralazine
• Association with sex hormone (more in female)
• Trigger by exposure to sun light

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SLE Atiology

• Immunologic Factors
• Polyclonal B-cell activation?
• Oligoclonal B-cell activation
• CD4 T helper cell activation

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SLE mechanism of tissue injury

• Immune complex disease
• Example deposition of Ag-Ab complex in glomeruli
  results in kidney disease
• Type II hypersensitivity
• Hemolysis
• Thrombocytopenia

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SLE common clinical manifestations

• Hematologic anemia, leukopenia, thrombocytopenia
• Arthritis
• Skin rash
• Fever
• Fatigue
• Weight loss

• Renal disease
• CNS abnormality
• Pleuritis
• Myalgia
• Pericarditis
• GI inflammation
• Raynaud phenomenon
• Peripheral neuropathy

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Pathological Findings

• Ag-Ab complex deposition
• Common kidney, hear, vessels, serosal membranes,
  and skin
• With the consequences of inflammation and tissue
  injury

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Pathological Findings

• Vessels
• Acute necrotizing vasculitis
• Skin
• Rash, erythema
• Cell injury/necrosis of the basal layer of
  epidermis, edema, inflammation
• Deposition of Ig, complement components

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Pathological Findings

• Joints
• Inflammation of synuvium, edema, mononuclear cell
  infiltrate
• Spleen
• Enlargement with follicular hyperplasia
• Serosa pleura, peritoneum, pericardium
• Serous effusion
• Fibrinous inflammation
• fibrosis

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Pathological Findings

• Heart
• Pericarditis, myocarditis
• Valvular lesion Libman-Sacks endocarditis
• Coronary artery disease
• Kidney
• Deposition of complexes in glomeruli
• Lupus nephritis
• Cell injury/necrosis, proliferation of mesangium,
  endothelium, and epithelium

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